MET基因单核苷酸多态性与336例肝细胞癌患者术后生存期关联分析

Association between MET gene single nucleotide polymorphism and survival of in 336 patients with hepatocellular carcinoma after operation

目的探讨MET基因单核苷酸多态性(SNP)与肝细胞癌术后患者总生存期(OS)的关联。方法选取广西医科大学附属肿瘤医院2004-06-01-2013-12-31接受肝细胞癌根治术治疗的336例患者为研究对象,使用Sequenom Mass Array法对MET基因的4个SNP位点(rs121 A>G、rs38840 C>T、rs41739 A>G和rs6566 A>G)进行基因分型并利用乘积极限法(Kaplan-Meier)和Cox比例风险回归模型分析SNP位点基因型与肝细胞癌术后患者OS关系。结果饮酒(HR=1.36,95%CI为1.02~1.82,P=0.035)、吸烟(HR=1.33,95%CI为1.02~1.75,P=0.038)、巴塞罗那分期(HR=2.89,95%CI为2.22~3.76,P<0.001)、肿瘤直径(HR=1.77,95%CI为1.35~2.32,P<0.001)、是否发生癌栓(HR=2.15,95%CI为1.62~2.85,P<0.001)和高血压(HR=0.51,95%CI为0.28~0.94,P=0.031)均与肝细胞癌术后患者OS有统计学意义的关联,在单个SNP位点分析时,MET基因各SNP位点与肝细胞癌术后患者OS均无统计学意义的关联,均P>0.05。进一步分析SNP-SNP之间的联合作用,发现携带2~4个潜在风险基因型(简称风险基因型:rs1621 AA、rs38840 CT/TT、rs41739 AA和rs6566 AA)的肝细胞癌术后患者比携带0~1个风险基因型患者的中位生存时间(MST)缩短,差异有统计学意义,MST分别为25.83和30.29个月,P=0.017。Cox比例风险回归分析发现,携带2~4个风险基因型肝细胞癌术后患者发生死亡的风险是携带0~1个风险基因型患者的1.33倍,HR=1.33,95%CI为1.03~1.73,P=0.032,是肝细胞癌术后患者预后的独立危险因素。结论MET基因多态位点rs1621、rs38840、rs41739和rs6566的联合作用可能影响肝细胞癌术后患者的生存结局,其风险基因型的联合作用使肝细胞癌术后患者MST缩短。

Objective To explore the relationship between single nucleotide polymorphism(SNP)individually and jointly and overall survival(OS)of patients with hepatocellular carcinoma(HCC)after operation.Methods A total of 336 HCC patients with undergone radical surgery resection in the Guangxi Medical University Cancer Hospital from June 1,2004 to December 31,2013 were included in his study.Four candidate SNPs(rs1621 A>G),rs38840 C>T,rs41739 A>G and rs6566 A>G in MET were genotyped by Sequenom Mass Array,and used Kaplan-Meier analysis and Cox proportional hazards regression model to evaluate the effect of genotypes and OS.Results Drinking(HR=1.36,95%CI:1.02-1.82,P=0.035),smoking(HR=1.33,95%CI:1.02-1.75,P=0.038),BCLC staging(HR=2.89,95%CI:2.22-3.76,P<0.001),tumor diameter(HR=1.77,95%CI:1.35-2.32,P<0.001),cancer thrombus(HR=2.15,95%CI:1.62-2.85,P<0.001)and hypertension(HR=0.51,95%CI:0.28-0.94,P=0.031)were statistically correlated with OS in patients after hepatocellular carcinoma surgery.Based on the analysis of individual SNPs,no significant relation was found between these SNPs and the OS of HCC patients.Kaplan-Meier analysis showed a significantly shorter OS in patients with 2-4 risk genotypes than those with 0-1 risk genotypes(MST=25.83 months vs 30.29 months,P=0.017).Cox proportional hazard regression analysis found that patients with 2 to 4 risk genotypes were 1.33 times more likely to die after surgery for patients with 0 to 1 risk genotypes(HR=1.33,95%CI:1.03-1.73,P=0.032),it was an independent risk factor for the prognosis of patients with hepatocellular carcinoma after surgery.Conclusions Our results indicated that MET SNPs(rs1621 AA,rs38840 CT/TT,rs41739 AA and rs6566 AA)jointly affect the overall survival time of patients with HCC after operation,which may serve as an independent prognostic marker for patients with HCC after operation.